Genetic Influences on Circulating Vitamin D Level: A Review

Over the last decade, there has been renewed interest in vitamin D due to increasing evidence of its importance in a wide range of health outcomes in addition to its traditional role in bone health. Although environmental factors play important roles in determining vitamin D levels, recent large-scale genetic studies also confirmed strong genetic influences. Recent genome-wide association studies (GWAS) have found genetic variations associated with vitamin D metabolism on several genes such as 7 dehydrochlesterol reductase (DHCR7), vitamin D binding protein (GC), 25-hydroxlase (CYP2R1), and 24-hydroxylase (CYP24A1). Vitamin D receptor (VDR), 25-hydroxyvitamin D 1-α hydroxylase (CYP27B1) and another 25- and 24-hydroxylase (CYP3A4) have also shown significant association in various candidate gene studies. Despite recent success in genetic studies, currently identified genes could only explain a small fraction of genetic variation in 25-hydroxyvitamin D level. With advances in next generation sequencing technologies, additional genetic variants and epigenetic mechanisms are expected to further reveal the genetic architecture of vitamin D metabolism.